The influence of amino-acid supplementation, gestational age and time on thyroxine levels in premature neonates.

OBJECTIVE: Newborn screening laboratories vary in the values that are used to define congenital hypothyroidism. Defining congenital hypothyroidism is particularly complex in premature neonates because prematurely born infants often have a low free thyroxine value and low or normal TSH value, termed as transient hypothyroxinemia of prematurity. In a multicenter (n=11 sites) trial, we randomly allocated premature neonates with a gestational age of 23 to 29 and 6/7 weeks to one of two parenteral nutrition approaches. The primary objective of our trial was to measure the effect of two distinct strategies of parenteral nutrition on neonatal growth and blood amino acids. A protocol defined secondary aim of our clinical trial was the evaluation of the influence of gestational age, time and the degree of amino-acid supplementation on total thyroxine levels. We hypothesized that an increase of amino-acid supplementation would be associated with the normalization of serum amino acids and that this would improve thyroxine synthesis. STUDY DESIGN: Premature neonates (23 to 29 and 6/7 weeks) were randomly allocated to one of two approaches to intravenous amino-acid administration. In one group, amino-acid supplementation started at 1.0 g kg(-1) per day and advanced by 0.5 g kg(-1) per day to a maximum of 2.5 g kg(-1) per day (2.5 group). The other group received amino acids at 1.5 g kg(-1) per day and advanced by 1.0 g kg(-1) per day to a maximum of 3.5 g kg(-1) per day (3.5 group). Filter paper blood spots were obtained on the day of randomization, and on days 7 and 28 of age to monitor laboratory values. RESULT: Enrollment included 122 neonates, 64 in the 3.5 group and 58 in the 2.5 group. There were no differences in demographics or baseline characteristics between the two treatment groups. There were no significant differences in thyroid levels at baseline, on days 7 and 28 between the two treatment groups. Growth was similar in both groups. It was noted that thyroxine levels changed over time and that the changes with time were greatest in the most preterm neonates. CONCLUSION: The degree of amino-acid supplementation does not influence thyroxine levels and both time from birth and gestational age do influence thyroxine levels.

Demographic and nutritional factors associated with prolonged cholestatic jaundice in the premature infant.

OBJECTIVE: The primary aim of this study was to determine if an association exists between amino-acid levels and development of cholestasis. The secondary aim of our amino-acid dose comparison trial was to identify factors associated with the development of prolonged cholestatic jaundice. STUDY DESIGN: We compared demographic characteristics and amino-acid levels in neonates who developed cholestasis with those who did not. Parenteral-associated cholestatic liver disease was defined as a direct serum bilirubin above 5 mg per 100 ml any time during the first 28 days after birth in neonates with no history of biliary atresia or viral hepatitis. We obtained filter paper blood spots for amino acid and acylcarnitine measurements on the day of randomization and days 7 and 28 of age to identify a profile of values that could be used to identify neonates with evidence of abnormal liver function. RESULT: We enrolled 122 neonates in our study; 13 (10.7%) developed cholestasis. Neonates who developed cholestasis were more immature, had lower birth weight, were exposed to parenteral nutrition for a longer period, had a higher cumulative dose of amino acids, were less often on enteral nutrition by day 7 of age, more often had a patent ductus arteriosus and severe intraventricular hemorrhage and were more commonly treated with steroids by 28 days of age. Amino acid and acylcarnitine values were not different for the two groups on the day of randomization. On day 7 (parenteral phase of nutrition), blood urea nitrogen, citrulline, histidine, methionine and succinyl carnitine were higher, and serine, glutamate and thyroxine levels were lower in the neonates who developed cholestasis than in who did not. CONCLUSION: Cholestasis remains an important complication of parenteral nutrition, and several clinical and biochemical factors may be helpful in identifying high-risk patients.

Role of multiple site blood cultures to document the clearance of bacteremia in neonates.

OBJECTIVE: To evaluate the usefulness of two-site blood cultures for the documentation of bacterial clearance during initial treatment of culture proven neonatal sepsis. DESIGN/METHODS: Clinical data were prospectively collected for 216 neonates who had blood cultures drawn for evaluation of possible sepsis. A positive diagnostic blood culture was followed by repeat blood cultures from two different peripheral sites after initiation of antimicrobial therapy. RESULTS: Follow-up two-site cultures were drawn on 25 occasions at a median interval of 3 days after start of antimicrobial therapy for culture-proven sepsis in 15 neonates. On 12 occasions, follow-up blood cultures were both negative. On eight occasions, follow-up blood cultures grew the same organisms from both sites. However, follow-up two-site cultures on five occasions in four of the 15 infants grew organisms from one site but not the second site. CONCLUSIONS: Two-site blood cultures seem necessary to document bacterial clearance in response to antimicrobial therapy for culture-proven sepsis, and may help determine the appropriate duration of antimicrobial therapy by reducing false-negative results.

Impact of l-carnitine supplementation on metabolic profiles in premature infants.

OBJECTIVE: To describe the influence that of l-carnitine supplementation on acylcarnitine (AC) profiles and hospital outcomes in premature infants. STUDY DESIGN: This study is a secondary analysis of previously reported work. Metabolic profiles were obtained using standard newborn techniques on infants born between 23 and 31 completed weeks of gestation. The profiles were drawn within the first 24 h after birth and on approximately days 7, 28 and 42 of life, or at the time of discharge. A single, central, contract laboratory analyzed and managed the samples. RESULTS: We studied 995 patients; none was subsequently diagnosed with an inborn error of metabolism. l-Carnitine was added to parenteral nutrition in 390 (39%) study subjects; 592 (60%) did not receive supplementation. Non-supplemented infants were more likely to develop low levels of free carnitine (FC; <7 µm) on day 28; (41% vs 5%, P<0.01); and FC values were lower on day 7. Despite higher levels of FC and fewer patients with significant carnitine deficiencies, we found no evidence that l-carnitine supplementation was associated with improved short-term hospital outcomes. CONCLUSION: l-Carnitine supplementation is common in prematurely born neonates and is associated with higher carnitine levels, but is not associated with improved short-term hospital outcomes.

Anthropometric trends from 1997 to 2012 in infants born at ⩽28 weeks' gestation or less.

OBJECTIVE: Postnatal growth failure is common after preterm birth, in particular for infants born at ⩽28 weeks' gestation, but it is unknown if growth-to-term equivalent age has improved over the years as neonatal intensive care in general, and infant nutrition in particular, have improved. The objective of the study was to evaluate anthropometric trends at NICU discharge for infants born at ⩽28 weeks' gestation using a large national database. STUDY DESIGN: Analysis of growth in weight, length, head circumference and body mass index (kg m2) in 23 005 infants born in 1997 to 2012 who survived to neonatal intensive care unit discharge at ⩽41 weeks' postmenstrual age. RESULTS: Discharge weight, length, head circumference and body mass index were converted to Z-scores using a reference database, and growth trends over the 16 years were summarized. Discharge results also were summarized for common neonatal morbidities, including chronic lung disease. Gestational age at birth and postmenstrual age at discharge were similar across the 16 years. Discharge weight, length and head circumference Z-scores were all below the median, but head circumference Z-scores consistently were closer to the median than were weight and length. In 1997 compared with 2012, the weight Z-score improved from -1.5 to -0.6; the length Z-score increased the least, from -1.68 to just -1.16; the head circumference Z-score improved from -0.68 to -0.30; and the body mass index Z-score increased from -0.66 to 0.19. Percent small-for-gestational age at birth was stable across the years at 8.4 to 9.3%, and the frequency of postnatal growth failure at discharge improved from 55.4% in 1997 to 19.6% in 2012. CONCLUSIONS: Growth-to-discharge progressively improved from 1997 to 2012, but Z-scores remained below the reference median for weight, length and head circumference. Length Z-scores were consistently significantly less than for weight, and body mass index Z-scores have been above the reference median since 2002. Prospective studies are needed to quantify anthropometric trends in relation to body composition and to current nutritional strategies.

A study of the role of multiple site blood cultures in the evaluation of neonatal sepsis.

BACKGROUND: The optimal number of blood cultures needed to document sepsis in an ill neonate has undergone little critical evaluation. Multiple site cultures may improve pathogen detection if intermittent bacteremia occurs, or if a low density of bacteria is present in the blood. We hypothesized, however, that bacterial clearance is slower and bacteremia more continuous in septic neonates, so that a single site blood culture should be sufficient to accurately document true septicemia. OBJECTIVE: To determine the need for multiple site blood cultures in the evaluation of neonates for sepsis. DESIGN/METHODS: Clinical data were prospectively collected for 216 neonates who had 269 pairs of blood cultures taken from two different peripheral sites for the evaluation of possible sepsis. A minimum of 1 ml of blood was obtained from the two peripheral sites within 15-30 min of each other. Based on prior retrospective data, we determined that 203 infants would need to have two site blood cultures to demonstrate a significant improvement in pathogen detection at an alpha of 0.05 and a beta of 0.20 (80%) power. RESULTS: A total of 186 culture pairs were taken for evaluation of early-onset sepsis in 186 neonates, while 83 pairs were drawn for evaluation of late-onset sepsis in 43 neonates. In all, 21 neonates from the late-onset group were evaluated more than once, and 12 neonates were evaluated for both early- and late-onset sepsis. In all, 20 (9.2%) of 216 neonates had 22 episodes of culture-proven sepsis at a median age of 18 days. All neonates with positive cultures had the same organism with a similar sensitivity pattern obtained from the two different peripheral sites. The other 196 study neonates had negative blood cultures from both sites. The single episode of early-onset sepsis was caused by Listeria monocytogenes, while all remaining episodes were late-onset with the following organisms: Staphylococcus epidermidis (7), methicillin-resistant Staphylococcus aureus (MRSA) (3), combined MRSA and Candida albicans (2), Candida albicans alone (2), late-onset Group B beta-hemolytic Streptococcus (GBS) (2), Klebsiella pneumoniae (2), Enterococcus fecalis (1), Escherichia coli (1), and Serratia marcescens (1). Since no infant grew organisms from only one of the two sites, the data indicate that the diagnosis of sepsis would have been made correctly in all infants with a single site culture. CONCLUSIONS: Two site blood cultures for the initial evaluation of neonatal sepsis do not have a better yield in pathogen detection. Sepsis in neonates can be detected with no loss of accuracy with a single site blood culture with blood volume of>or=1 ml.

The epidemiology, prevalence and hospital outcomes of infants with gastroschisis.

OBJECTIVE: The purpose of this study is to evaluate recent trends in prevalence of gastroschisis among infants admitted for neonatal intensive care in the United States. STUDY DESIGN: Retrospective review of a de-identified patient data. The current study extends our observations through the end of 2007 to 2015. RESULTS: During the study period (1 January 1997 to 12 December 2015), there were 1 158 755 total discharges; 6023 (5.2/1000) had gastroschisis and 1885 (1.6/1000) had an omphalocele. Between 1997 and 2008, the reported rate of gastroschisis increased from 2.9 to 6.4/1000 discharges. From 2008 to 2011, the values have slowly decreased from 6.4 to 4.7/1000 discharges and since 2011 have been stable. The largest drop in the prevalence was in mothers who were <20 years old. In contrast, the reported rate of omphalocele was stable at 1 to 2/1000 discharges. CONCLUSION: The prevalence of gastroschisis increased from 1997 to 2008, and then declined thereafter.

Quantitative computer analysis of the sounds of isolated motor unit action potentials.

To develop quantitative measures of motor unit action potential (MUAP) sounds, we correlated Fourier domain features of isolated, individual MUAPs with classic time domain measurements. There were moderate correlations between amplitude or duration measurements, and absolute low-frequency (39 to 234 Hz) energy and amplitude of the peak frequency, and high correlations between the composite time domain feature of amplitude x duration, and total energy, amplitude of the peak frequency, and absolute low-frequency energy. Polyphasic potentials have multiple peaks in the magnitude component of the Fourier transform. Phase information appears to convey the "crisp" sound of MUAPs close to the recording electrode. The clinical description of "large" or "small" MUAPs by sound is likely based on absolute low-frequency energy, and incorporates both amplitude and duration information. We conclude that features of isolated MUAPs may be analyzed in the Fourier domain, and that they correlate closely with traditionally used measures of known diagnostic significance. The sound of the EMG used by clinical electromyographers is amenable to quantitative analysis.

Pulmonary mechanics in preterm neonates with respiratory failure treated with high-frequency oscillatory ventilation compared with conventional mechanical ventilation.

Pulmonary mechanics were measured in 43 preterm neonates (mean +/- SD values of birth weight 1.2 +/- 0.3 kg, gestational age 30 +/- 2 weeks) with respiratory failure who were concurrently randomly assigned to receive conventional mechanical ventilation (n = 22) or high-frequency ventilation (n = 21). The incidence of bronchopulmonary dysplasia was comparable in the two groups (high-frequency ventilation 57%, conventional ventilation 50%). Pulmonary functions were determined at 0.5, 1.0, 2.0, and 4.0 weeks postnatal ages. Data were collected while subjects were in a nonsedated state during spontaneous breathing. These sequential data show similar patterns of change in pulmonary mechanics during high-frequency ventilation and conventional mechanical ventilation irrespective of gestational age, birth weight stratification, or bronchopulmonary dysplasia. There was no significant difference in the pulmonary functions with either mode of ventilation during the acute phase (less than or equal to 4 weeks) of respiratory disease. When evaluated by the clinical diagnosis of bronchopulmonary dysplasia, the pulmonary data suggested a less severe dysfunction in the high-frequency oscillatory ventilation-treated bronchopulmonary dysplasia group compared with the conventional mechanical ventilation-treated group. These results indicate that high-frequency oscillatory ventilation in preterm neonates does not reduce the risk of acute lung injury; however, the magnitude of the pulmonary dysfunction in the first 2 weeks of life merits a reevaluation.

No lumbar puncture in the evaluation for early neonatal sepsis: will meningitis be missed?

OBJECTIVE: We performed this investigation to assess whether selective approaches to performing lumbar puncture (LP) in the early neonatal period will result in a missed or delayed diagnosis of bacterial meningitis. DESIGN: A retrospective review was conducted of the medical records of all neonates born in US Army hospitals from 1988 through 1992 who developed culture-positive meningitis during the first 72 hours of life. RESULTS: In total, 169,849 infants were born during the 5-year study period. The incidence of meningitis in the first 72 hours of life was 0.25 per 1000 live births. Forty-three infants had organisms isolated from their cerebrospinal fluid (30, group B streptococcus; 10, Escherichia coli; 1, Listeria monocytogenes; 1, Streptococcus pneumoniae; and 1, Citrobacter diversus). The median age of infants at evaluation was 12 hours, and the mean gestational age was 38.8 weeks (7 < 37 weeks), whereas mean birth weight was 3163 g (7 < 2500 g). If we had used currently advocated selective criteria as the basis for not performing an LP, the diagnosis of bacterial meningitis would have been missed or delayed in 16 of 43 infants (37%): 5 infants born prematurely with suspected respiratory distress syndrome, 3 asymptomatic infants born at term with positive blood cultures, and 8 infants born at term with no central nervous system symptoms and negative blood cultures. CONCLUSIONS: If LPs are omitted as part of the early neonatal sepsis evaluation, the diagnosis of bacterial meningitis occasionally will be delayed or missed completely.

Infant sleep position following new AAP guidelines. American Academy of Pediatrics.

OBJECTIVE: This report examines the response of families to the American Academy of Pediatrics June 1992 recommendation that healthy term infants be put to sleep on their back or side to decrease the risk of sudden infant death syndrome. Parents at two clinics and private practices were interviewed to ascertain sleep position practices. METHODS: Parents of infants from 1 to 6 months of age who were in the waiting room for a well-child visit were eligible for study. A total of 760 interviews were conducted using a closed-ended questionnaire. Parents were asked about sleep position, positional changes during sleep, and factors that influenced their decision to position their infant prone, side, or supine. Interviews were conducted from September 1993 through April 1994. This interval was divided into two equal, 4-month time intervals. Sleep practices were compared during the first and second time periods. Differences between practice and clinic groups were measured. Groups were compared using the chi-square test, with results considered significant at P < .05. RESULTS: The number of infants placed side or supine for sleep increased significantly since the inception of the study, from 38.1% to 59.1%. Despite this increase, parents reported that the impetus for changing position came from family or the media, rather than from health professionals. Initially, the proportion of infants in private practices placed side or supine was greater than that of clinic patients. That difference disappeared by the end of the study. Prone positioning continued to be more prevalent in the 3- to 6-month-old infants than in the 1- to 3-month-old group. The majority of infants at all ages awoke in the same position that they were put to sleep. CONCLUSIONS: Side and supine positioning for sleep increased in all socioeconomic groups. A small number of infants placed side or supine for sleep are found prone on awakening. Health professionals need to increase their role in providing sleep position guidance. As the proportion of the population positioning their infants side or supine for sleep increases, it should be possible to examine the effect on the sudden infant death syndrome rate.

Diagnosis-related criteria in the consideration of extracorporeal membrane oxygenation in neonates previously treated with high-frequency jet ventilation.

High-frequency jet ventilation (HFJV) is one of several high-frequency techniques that are particularly valuable for treating the neonate with lung disease refractory to conventional ventilation or with pulmonary air leak. Extracorporeal membrane oxygenation (ECMO) has also emerged as a valuable rescue therapy for neonates of more than 2000 g birth weight and 34 weeks' gestation with intractable respiratory failure. With the concurrent introduction of HFJV and ECMO, the authors sought to evaluate the role of HFJV prior to the institution of ECMO therapy. The data base for 2856 neonates receiving mechanical ventilation in one unit was used to identify 73 (of 298 total) neonates treated with HFJV, who were eligible by age and weight criteria for ECMO. Patients were grouped by diagnosis, and the oxygenation index (OI) was calculated during therapy. Outcome was evaluated for mortality, and the sensitivity of the OI for predicting mortality was calculated. Neonates who survived with HFJV alone presented with an OI of 0.30 +/- 0.03 (SEM), significantly less than nonsurvivors (0.42 +/- 0.04, P = .016). Survivors responded to HFJV with a rapid decrease in OI at 1 hour (0.19 +/- 0.02, P less than .001) and 6 hours (0.15 +/- 0.01, P less than .001). Nonsurvivors did not respond significantly at 1 hour (OI = 0.33 +/- 0.04, P = not significant [NS]) or at 6 hours (OI = 0.40 +/- 0.06, P = NS). By diagnosis, neonates with respiratory distress syndrome survived more often with HFJV (28/34, 82%) than neonates with meconium aspiration (10/26, 38%) or diaphragmatic hernia (3/9, 33%). Neonates with respiratory distress syndrome seldom presented with high OI values, but the majority of those who did survived (5/7 survived with initial OI greater than or equal to 0.40).(ABSTRACT TRUNCATED AT 250 WORDS)

Mechanical ventilation in preterm infants: neurosonographic and developmental studies.

Surviving preterm infants of less than 34 weeks' gestation who were selected on the basis of serial cranial ultrasonographic findings during their nursery course had repeated neurologic and developmental examinations during late infancy and early childhood that established the presence (n = 46) or absence (n = 205) of spastic forms of cerebral palsy. Of the 205 infants without cerebral palsy, 22 scored abnormally low on standardized developmental testing during early childhood. The need for mechanical ventilation beginning on the first day of life (n = 92) was significantly related to gestational age, birth weight, Apgar scores, patent ductus arteriosus, grade III/IV intracranial hemorrhage, large periventricular cysts, and the development of cerebral palsy. In the 192 mechanically ventilated infants, vaginal bleeding during the third trimester, low Apgar scores, and maximally low PCO2 values during the first 3 days of life were significantly related to large periventricular cysts (n = 41) and cerebral palsy (n = 43), but not to developmental delay in the absence of cerebral palsy (n = 18). The severity of intracranial hemorrhage in mechanically ventilated infants was significantly associated with gestational age and maximally low measurements of PCO2 and pH, but not with Apgar scores or maximally low measurements of PO2. Logistic regression analyses controlling for possible confounding variables disclosed that PCO2 values of less than 17 mm Hg during the first 3 days of life in mechanically ventilated infants were associated with a significantly increased risk of moderate to severe periventricular echodensity, large periventricular cysts, grade III/IV intracranial hemorrhage, and cerebral palsy. Neurosonographic abnormalities were highly predictive of cerebral palsy independent of PCO2 measurements.(ABSTRACT TRUNCATED AT 250 WORDS)

High-frequency jet ventilation in the early management of respiratory distress syndrome is associated with a greater risk for adverse outcomes.

OBJECTIVE: The objective of this investigation was to determine if high-frequency jet ventilation (HFJV) used early in the treatment of premature infants with respiratory distress syndrome was effective in reducing pulmonary morbidity without increasing the occurrence of adverse neurologic outcomes. STUDY DESIGN: A total of 73 premature infants who met the inclusion criteria (gestational age of less than 33 weeks, birth weight of more than 500 g, age of less than 24 hours, need for assisted ventilation with peak inspiratory pressure of more than 16 and FIO2 more than 0.30, and roentgenographic evidence of respiratory distress syndrome) were randomized to either conventional (n = 36) or to high-frequency jet (n = 37) ventilation. Our goals were to maintain the infants on the assigned ventilator for at least 7 days unless they could either be extubated or meet crossover criteria. Univariate analyses were initially used to compare the two groups. Stepwise logistic regression was subsequently used to assess whether various factors independently influenced adverse outcomes. RESULTS: The two groups of infants were similar in all obstetrical, perinatal, and neonatal demographic characteristics. The mean birth weight and gestational age in the conventional group were 930 g and 26.6 weeks and in the HFJV group, 961 g and 26.9 weeks. The infants were randomized at similar ages (7.1 and 7.3 hours of life, respectively). Their prerandomization ventilator settings and arterial blood gases were nearly identical. There were no differences in pulmonary outcomes (occurrence of air leaks, need for oxygen or ventilation at 36 weeks postconception), and there were no differences in the mean number of days oxygen was required, number of days ventilated, or length of hospital stay. Infants ventilated with HFJV were significantly more likely to develop cystic periventricular leukomalacia (10 vs 2, P = .022) or to have a poor outcome (grade IV hemorrhage, cystic periventricular leukomalacia, or death) (17 vs 7, P = .016). Logistic regression analysis revealed HFJV to be a significant independent predictor of both cystic periventricular leukomalacia and a poor outcome. The presence of hypocarbia was not an independently significant predictor of adverse outcomes. CONCLUSIONS: With the HFJV treatment strategy that we used, use of the high-frequency jet ventilator in the early management of premature infants with respiratory distress syndrome resulted in significantly more adverse outcomes than in those treated with conventional mechanical ventilation.

Effects of hypocarbia on the development of cystic periventricular leukomalacia in premature infants treated with high-frequency jet ventilation.

BACKGROUND AND OBJECTIVE: Previous data from our institution indicate that mechanically ventilated premature infants are at increased risk for cystic periventricular leukomalacia (CPVL), particularly if hypocapnia occurs. High-frequency jet ventilation (HFJV) may produce substantial hypocapnia. We sought to investigate whether hypocapnia during HFJV is associated with the development of CPVL. METHODS: Sixty-seven premature infants (mean gestational age, 27.2 weeks; mean birth weight, 1001 g) underwent HFJV for a mean of 44 (range, 8 to 70) hours during the first 3 days of life. All infants were followed with serial neurosonograms at least weekly until 6 to 8 weeks of age and every 2 to 4 weeks thereafter until discharge. To assess the cumulative effects of hypotension, acidosis, hypoxemia, and hypocarbia during the first 3 days of life on the development of PVL, we developed a quantitative assessment in which we assigned threshold levels at particular critical values of these parameters (such as a mean PaCO2 of 20 mm Hg) and calculated an area above the curve between longitudinally connected values of these parameters and the threshold levels. RESULTS: Nine of the 67 infants died before 21 days of life. Of the 58 who survived beyond 21 days, large CPVL (> 5 mm in size) developed in 18 infants. Infants with cysts were similar in birth weight, gestational age, and virtually all other antepartum, intrapartum, and postpartum parameters compared with the 40 neonates in whom CPVL did not develop. However, infants with CPVL were significantly more likely to have moderate or severe periventricular echodensities preceding development of CPVL and periventricular echodensities that persisted for a longer period. We did not find an effect of hypotension, acidosis, or hypoxemia on the development of CPVL. There were no differences in the mean PaCO2, the absolute low PaCO2 values, the ranges of low PaCO2 between groups, or area above the curve measurements at threshold levels of 15 and 20 mm Hg, respectively. However, logistic regression analysis revealed that infants with CPVL were independently significantly more likely to have greater cumulative hypocarbia below a threshold level of 25 mm Hg during the first day of life (odds ratio, 5.43; 95% confidence interval, 1.33 to 22.2). CONCLUSIONS: Hypocarbia produced by treatment with HFJV during the first 3 days of life is associated with the subsequent development of CPVL. The mechanisms for the development of CPVL among premature infants treated with HFJV need to be established.

Prognosis with preoperative pulmonary function and lung volume assessment in infants with congenital diaphragmatic hernia.

OBJECTIVES: To determine whether fatal pulmonary hypoplasia, as assessed by functional residual capacity (FRC), can be distinguished from other reversible causes of respiratory failure in infants with congenital diaphragmatic hernia (CDH). METHODS: In the present study, 25 term neonates having CDH without other anomalies (mean birth weight +/- SD, 3.25 +/- 0.50 kg) were enrolled prospectively into a protocol evaluating pulmonary function. Lung compliance (CL) and FRC were measured before diaphragmatic repair and compared with the highest oxygenation index (OI) and lowest PaCO2, also obtained preoperatively. Pulmonary function assessment was repeated after diaphragm repair on postoperative days 3 and 7. CL was determined by esophageal manometry and pneumotachography, and FRC was determined by helium dilution. RESULTS: Fifteen infants (60%) survived to hospital discharge. Eighteen (72%) required extracorporeal membrane oxygenation (ECMO) for support, and of these, 8 (44%) survived. PaCO2 was similar preoperatively in infants grouped as survivors without ECMO, survivors with ECMO, and nonsurvivors. In nonsurvivors (all of whom received ECMO), the preoperative OI was significantly higher (51 +/- 21), CL was less (0.11 +/- 0.04 mL/cm of water per kg), and FRC was smaller (4.5 +/- 1.0 mL/kg) than in the survivors who required ECMO (26 +/- 18, 0.18 +/- 0.08 mL/cm of water per kg, and 12 +/- 5 mL/kg, respectively), as well as in the survivors without ECMO, (6 +/- 2, 0.32 +/- 0.16 mL/cm of water per kg, and 15.8 +/- 4 mL/kg, respectively). The group surviving with ECMO had a higher OI than the infants surviving without ECMO. All nonsurviving infants had FRCs of less than 9.0 mL/kg preoperatively. In contrast, only 2 of the 15 survivors had preoperative FRCs less than 9 mL/kg. CONCLUSIONS: The results of this study suggest that preoperative assessment of FRC may predict fatal pulmonary hypoplasia in most infants with CDH.

Brain SPECT in neonates following extracorporeal membrane oxygenation: evaluation of technique and preliminary results.

Extracorporeal membrane oxygenation (ECMO) is a life-saving procedure in neonates with refractory respiratory failure that has been used at our institution since 1985. In an attempt to study its clinical value, regional cerebral blood flow (rCBF) alterations were measured using SPECT and 99mTc-HMPAO in 13 newborns following ECMO. Eight infants were studied after ECMO with reanastomosis of the right common carotid artery (RCCA), two with the permanent ligation of the RCCA, and three after veno-venous ECMO. Brain SPECT was technically satisfactory in all newborns using a triple-head SPECT system. Altered rCBF was found in 7 of 13 infants. In five newborns, there was a decrease in rCBF within the ipsilateral hemisphere, and in one infant, contralateral hemisphere was involved. In one infant, there was bilateral hemispheric involvement. The infant underwent cardiopulmonary resuscitation prior to ECMO and exhibited clinical features of hypoxicischemic encephalopathy at the time of SPECT. Only 2 of 13 newborns demonstrated morphologic changes on neuroimaging modalities such as cranial ultrasonography, computed tomography and magnetic resonance imaging. Our study demonstrates that: (1) functional brain imaging is feasible in neonates after ECMO; (2) SPECT has potential for demonstrating rCBF deficits not detectable by neuroanatomic imaging modalities; and (3) SPECT has potential clinical value in long-term follow-up of neurodevelopmental outcome after ECMO.

Activation of protein kinase C by 1,4-dihydro-2,6-dimethyl-5-nitro-4-[2-(trifluoromethyl)-phenyl]-3-py rid ine carboxylic acid methyl ester (Bay K 8644), a calcium channel agonist, in alveolar type II cells.

A role for calcium channels in the regulation of surfactant secretion is suggested by the observation that endothelin-1-stimulated surfactant secretion is inhibited by calcium channel blockers. 1,4-Dihydro-2,6-dimethyl-5-nitro-4-[2-(trifluoromethyl)-phenyl]-3-pyridi ne carboxylic acid methyl ester (Bay K 8644), a dihydropyridine derivative, stimulates voltage-dependent and non-voltage-dependent calcium channels in a number of cell types. This study demonstrates that Bay K 8644 increased phosphatidylcholine (PC) secretion in isolated lung epithelial type II cells in a time- and concentration-dependent manner with an EC50 of 100 +/- 8 nM (mean +/- SEM, N = 6). The secretagogue effect of Bay K 8644 was independently decreased in the absence of external calcium, or in the presence of nifedipine, a calcium channel antagonist, or inhibitors of protein kinase C (PKC). Bay K 8644 increased intracellular calcium from 130 +/- 8 to 230 +/- 14 nM (N = 6, P < 0.05), an effect that was blocked by nifedipine. Bay K 8644 also increased the membrane-associated PKC activity in a concentration-dependent manner. In the membranes from Bay K 8644-stimulated cells, the increase in calcium-dependent PKC was greater than that in the calcium-independent PKC, suggesting preferential translocation of calcium-dependent PKC to the membranes. We suggest that both elevated calcium and activation of PKC are required for calcium agonist Bay K 8644-induced surfactant secretion in type II cells.

Risk factors for bronchopulmonary dysplasia after extracorporeal membrane oxygenation.

OBJECTIVE: To determine risk factors for the development of bronchopulmonary dysplasia (BPD) after treatment with extracorporeal membrane oxygenation (ECMO). DESIGN: Retrospective case-control study. SETTING: Tertiary care level 3 neonatal intensive care unit. PARTICIPANTS: Seventy-three newborns treated with ECMO for severe respiratory failure during a 5-year period, who survived until day of life 28, and who did not have pulmonary hypoplasia as the initial cause for respiratory failure. INTERVENTIONS: None. MAIN OUTCOME MEASURE: The presence of BPD after treatment with ECMO, which was defined as oxygen and/or ventilatory requirements at day of life 28, with characteristic abnormalities seen on chest x-ray film. RESULTS: The age at ECMO initiation was significantly greater for patients with BPD compared with patients without BPD (mean +/- SD, 135 +/- 68 hours vs 50 +/- 37 hours; P < .001). There was an 11.5-fold increased risk for the development of BPD if ECMO was initiated at greater than 96 hours of age. The primary diagnosis of respiratory distress syndrome imparted a 5.2-fold increased risk for the development of BPD. Patients with BPD required ECMO significantly longer than patients without BPD (203 +/- 73 hours vs 122 +/- 51 hours; P < .001). CONCLUSION: These results demonstrate that delayed use of ECMO in treating neonatal respiratory failure is associated with an increased risk for the development of BPD and a longer duration of ECMO therapy.

Ventilatory response to combined high frequency jet ventilation and conventional mechanical ventilation for the rescue treatment of severe neonatal lung disease.

High frequency jet ventilation (HFJV) was used to treat 176 infants who were either failing to respond to conventional mechanical ventilation (CMV) or demonstrating pulmonary air leak. The median birthweight for infants treated with HFJV was 1530 g, median gestational age was 31 weeks. Median duration of therapy with HFJV was 3.0, with a range of 0.1 to 27 days. During the first 24 hours of treatment, mean airway pressure decreased from 16.2 +/- 0.3 (Mean +/- SEM) cmH2O to 12.2 +/- 0.3 cmH2O, while mean PaO2 increased from 65.3 +/- 3.0 torr to 93.3 +/- 3.0 torr during the same time period. Simultaneously, mean PaCO2 decreased from 46.4 +/- 1.5 torr to 36.6 +/- 1.0 torr, although peak inflating pressure decreased from 34.3 +/- 0.7 cmH2O to 30.1 +/- 0.8 cmH2O. Ninety-five (54%) infants treated with HFJV survived. Of 123 infants with RDS 75 (61%) survived. The rate of complications for HFJV patients was similar to that seen with CMV in our nursery. This study suggests that HFJV provides improved oxygenation and ventilation of infants at lower mean and peak pressures compared to conventional mechanical ventilation. HFJV combined with CMV may be a valuable adjunct to therapy in infants with severe lung disease.